Synthesis 2019; 51(18): 3471-3476
DOI: 10.1055/s-0037-1611566
paper
© Georg Thieme Verlag Stuttgart · New York

Total Syntheses of (–)-7-epi-Alexine and (+)-Alexine Using Stereoselective Allylation

In-Soo Myeong
a   School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Suwon-si, Gyeonggi-do 16419, Republic of Korea   Email: whham@skku.edu
,
Changyoung Jung
a   School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Suwon-si, Gyeonggi-do 16419, Republic of Korea   Email: whham@skku.edu
,
Won-Hun Ham*
a   School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Suwon-si, Gyeonggi-do 16419, Republic of Korea   Email: whham@skku.edu
b   Yonsung Fine Chemicals Co., Ltd., Sujeong-ro 207, Jangan-myeon, Hwaseong-si, Gyeonggi-do 18581, Republic of Korea
› Author Affiliations
This work was supported by Yonsung Fine Chemicals Co., Ltd.
Further Information

Publication History

Received: 11 April 2019

Accepted after revision: 09 May 2019

Publication Date:
12 June 2019 (online)


Abstract

Total syntheses of (–)-7-epi-alexine and (+)-alexine were achieved by using stereoselective allylation via a functionalized pyrrolidine obtained from an extended chiral 1,3-oxazine. The synthetic strategies include pyrrolidine formation via oxazine cleavage and diastereoselective allylations of a pyrrolidine aldehyde. (–)-7-epi-Alexine and (+)-alexine were synthesized from anti,syn,anti-oxazine in 12 steps.

Supporting Information

 
  • References

    • 1a Myeong I.-S, Jung C, Kim J.-Y, Park S.-H, Ham W.-H. Tetrahedron Lett. 2018; 59: 2422
    • 1b Myeong I.-S, Kim J.-S, Lee Y.-T, Kang J.-C, Park S.-H, Jung C, Ham W.-H. Tetrahedron: Asymmetry 2016; 27: 823
    • 1c Kim J.-S, Lee Y.-T, Lee K.-H, Myeong I.-S, Kang J.-C, Jung C, Park S.-H, Ham W.-H. J. Org. Chem. 2016; 81: 7432
    • 1d Kim J.-S, Kim G.-W, Kang J.-C, Myeong I.-S, Jung C, Lee Y.-T, Choo G.-H, Park S.-H, Lee G.-J, Ham W.-H. Tetrahedron: Asymmetry 2016; 27: 171
    • 1e Park S.-H, Kim J.-Y, Kim J.-S, Jung C, Song D.-K, Ham W.-H. Tetrahedron: Asymmetry 2015; 26: 657
    • 1f Park S.-H, Jin X, Kang J.-C, Jung C, Kim S.-S, Kim S.-S, Lee K.-Y, Ham W.-H. Org. Biomol. Chem. 2015; 13: 4539
    • 1g Kim J.-S, Kang J.-C, Yoo G.-H, Jin X, Myeong I.-S, Oh C.-Y, Ham W.-H. Tetrahedron 2015; 71: 2772
  • 2 Myeong IS, Ham WH. Eur. J. Org. Chem. 2019; 1077
  • 3 Nash R, Fellows L, Dring J, Fleet G, Derome A, Hamor T, Scofield A, Watkin D. Tetrahedron Lett. 1988; 29: 2487
    • 4a Asano N, Nash RJ, Molyneux RJ, Fleet GW. Tetrahedron: Asymmetry 2000; 11: 1645
    • 4b Winchester B, Fleet GW. Glycobiology 1992; 2: 199
    • 5a Scofield AM, Rossiter JT, Witham P, Kite GC, Nash RJ, Fellows LE. Phytochemistry 1990; 29: 107
    • 5b Nash RJ, Fellows LE, Dring JV, Fleet GW, Girdhar A, Ramsden NG, Peach JM, Hegarty MP, Scofield AM. Phytochemistry 1990; 29: 111
    • 5c Elbein AD, Tropea JE, Molyneux RJ. US Pat. Appl. US 289907; Chem. Abstr. 1990; 113: P91444p
    • 5d Elbein AD. Annu. Rev. Biochem. 1987; 56: 497
    • 5e Legler G. Adv. Carbohydr. Chem. Biochem. 1990; 48: 319
    • 6a Yu L, Somfai P. RSC Adv. 2019; 9: 2799
    • 6b Dressel M, Restorp P, Somfai P. Chem. Eur. J. 2008; 14: 3072
    • 6c O’Riordan TJ. Org. Biomol. Chem. 2008; 6: 3896
    • 6d Takahashi M, Maehara T, Sengoku T, Fujita N, Takabe K, Yoda H. Tetrahedron 2008; 64: 5254
    • 6e Romero A, Wong C.-H. J. Org. Chem. 2000; 65: 8264
    • 6f Pearson WH, Hines JV. J. Org. Chem. 2000; 65: 5785
    • 6g Yoda H, Katoh H, Takabe K. Tetrahedron Lett. 2000; 41: 7661
    • 7a Pham V.-T, Joo J.-E, Lee K.-Y, Kim T.-W, Mu Y, Ham W.-H. Tetrahedron 2010; 66: 2123
    • 7b Kim J.-Y, Mu Y, Jin X, Park S.-H, Pham V.-T, Song D.-K, Lee K.-Y, Ham W.-H. Tetrahedron 2011; 67: 9426
  • 8 Chowdhury PS, Kumar P. Eur. J. Org. Chem. 2013; 4586
  • 9 Alcaraz L, Harnett J, Mioskowski C, Martel J, Le Gall T, Shin D.-s, Falck J. Tetrahedron Lett. 1994; 35: 5449
  • 11 Carreira EM, Du Bois J. J. Am. Chem. Soc. 1995; 117: 8106
  • 12 Peaks in 1H NMR and 13C NMR spectra of compounds are broad and split due to the presence of N-Cbz rotamers.